This is a competitive renewal application for the Lowell P. Weicker Jr. General Clinical Research Center (GCRC), which was established at the University of Connecticut Health Center (UCHC) in December, 1993. During its initial four years, the GCRC has grown substantially as a central outpatient facility. While over 90% of our studies are with outpatients, inpatient studies have been carried out using beds on a designated medical-surgical unit or a specialized unit, such as the Boone Marrow Transplant Unit or the Adult and Neonatal Intensive Care Units of UCHC.. This renewal application contains 37 research protocols, compared to 23 in the initial application. The emphasis in this application continued to be on studies involving interactions between basic scientists and clinical investigators, particular in the application of new methods of molecular biology and human genetics to the study of the pathogenesis of disease. The protocols in this renewal application cover a wide range, including studies on 1) alcohol and substance abuse, 2) osteoporosis and metabolic bone disease, 3) neurologic changes associated with HIV, 4) neurologic complications of tick-borne infections, 5) genetics of schizophrenia, 6) pathogenesis of heart failure, 7) immunotherapy for cancer and scleroderma, 8) pathogenesis of prostatitis, 9) oral mucositis in bone Sjogren's syndrome. The GCRC has become a major center for training. GCRC staff have developed an introductory course on methods of clinical research and offered new student electives. UCHC continues to make a substantial commitment to support the GCRC by providing funding for infrastructure. Moreover, additional space has been provided to allow for expansion of our facilities. The GCRC has shown continuous growth in clinical research activity and productivity. The proposed research should enhance our understanding of pathogenesis and increase our ability to treat conditions which affect large numbers of Americans.